2013 Grants - De Lago

Role of the Endocannabinoid System in TDP43-Related Dementia

2013 New Investigator Research Grant

TDP43 (TAR DNA binding protein-43) is a protein linked to several brain diseases. Abnormal forms of TDP43 are found in people who have Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease) and frontotemporal dementia. Each of these conditions is characterized by inflammation and degeneration of nerve cells.

Using mice genetically altered to have abnormal TDP43, the researchers plan to determine if this genetic change causes alterations in the endocannabinoid system. The endocannabinoid system refers to the ability of some nerve cells in the brain to respond to a class of drugs known as cannabinoids. Cannabinoids can come from external sources (such as cannabis) or from naturally occurring molecules in the brain (endocannabinoids). Several studies have shown that activation of the endocannabinoid system in the brain can reduce inflammation and potentially reduce damage to nerve cells.

Eva De Lago, Ph.D. and colleagues have proposed to study if drugs activating the endocannabinoid system can protect against nerve cell damage in animals with abnormal TDP43. They will then study whether cannabinoid drugs protect the brain from damage related to abnormal TDP43. These studies will help to determine whether cannabinoids may be worth further study for slowing or preventing progression of Alzheimer's disease and several related conditions.